Oncogene addiction in gliomas: Implications for molecular targeted therapy

Cancer arises as a result of a stepwise accumulation of genetic aberrations [1]. Despite multiple genetic alterations, its growth and survival can often be impaired by the inactivation of a single oncogene. This phenomenon indicates that tumors may become dependent upon a single oncogenic activity for both maintenance of the malignant phenotype and cell survival [2]. The phrase "oncogene addiction" was coined by Bernard Weinstein to describe the observation that tumor maintenance often depends on the continued activity of certain oncogene or loss of tumor suppressor gene [3]. Oncogene addiction provides a rationale for molecular targeted therapy in cancers [4]. More and more researches proposed that decoding of the oncogene addiction in cancer may provide a key for effective cancer therapy. But it is difficult to define oncogene addiction in numerous conditions. And the efficacy of this strategy requires novel methods, including integrative genomics and systems biology, to identify the status of oncogene addiction in individual cancer [3]. However, it has been known that so many growth related pathways are activated in cancers. To date, it remains controversial whether the cancer cells could get hooked on one single gene [5]. Although the debate that one gene shouldn't affect it much is still continuing, it is remarkable that in some cases reversing only one of these genes can have a strong inhibitory effect. Evidence that supports the concept of oncogene addiction has been obtained in various human cancers via Pubmed Search as indicated in Table 1[6-19].Glioma is the most common primary brain tumor in adults with poor prognosis [20]. The clinical outcomes of patients with glioma traditionally depend upon the tumor pathological grade. But the patients even within the same grade usually have diverse prognosis and therapeutic outcomes [21]. Over the last decade, the knowledge on the molecular genetic background of human gliomas has dramatically increased [22]. However